A metal complex that binds α-amino acids with high and predictable stereospecificity
A metal complex that binds α-amino acids with high and predictable stereospecificity
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作者：
Chin, J;Lee, SS;Kim, DH
分子识别是广泛的受控分离和化学转化过程中的关键步骤，酶以无与伦比的选择性执行此任务。酶只含有20个简单的氨基酸，但仍然很难合理化，甚至预测这些立体特异性识别事件。尽管如此，能够立体特异性识别氨基酸的受体的合理设计吸引了相当大的兴趣，因为可以从手性氨基酸中间体开发的治疗药物越来越需要对映体纯形式（1）。早期的工作（2-4）已经刺激了基于小分子的有效受体的开发（5-8），但是具有高和可预测的立体特异性的氨基酸结合仍然难以实现。另一方面，定向分子进化（9）确实选择了以高特异性结合氨基酸的RNA序列或抗体（10-12），但通常没有提供对所涉及的分子识别机制的见解。在这里，我们表明，一个合理设计的金属络合物形成的三价钴离子和四齿配体结合天然氨基酸，包括简单而具有挑战性的氨基酸丙氨酸，具有高和可预测的区域和立体特异性。我们期望我们的方法将允许其靶氨基酸的结合以及分离和立体特异性催化形成。
Molecular recognition is the key step in a wide range of controlled separation and chemical transformation processes, with enzymes performing this task with an unsurpassed degree of selectivity. Enzymes contain only 20 simple amino acids, yet it remains difficult to rationalize or even predict these stereospecific recognition events. Nonetheless, the rational design of receptors able to recognize amino acids stereospecifically is attracting considerable interest because therapeutic drugs, that may be developed from chiral amino acid intermediates, are increasingly required in enantiomerically pure form(1). Early work(2-4) has stimulated the development of efficient receptors based on small molecules(5-8), but binding of amino acids with high and predictable stereospecificity remains difficult to achieve. Directed molecular evolution(9), on the other hand, does select for RNA sequences or antibodies that bind amino acids with high specificity(10-12), but typically without providing insights into the molecular recognition mechanisms involved. Here we show that a rationally designed metal complex formed from a trivalent cobalt ion and a tetradentate ligand binds natural amino acids, including the simple yet challenging amino acid alanine, with high and predictable regio- and stereospecificity. We expect that our approach will allow the binding as well as separation and stereospecific catalytic formation of its target amino acids.